The traditional concept that no regrowth of nerve processes occurs in the mammalian C.N.S. is being discarded in the light of new evidence. After hearing scientific reports, participants at a meeting on central nervous regeneration agreed that the problem of curing patients with C.N.S. lesions should not be considered insoluble (Meeting in Palm Beach, 1970, reported by Guth and Windle). What factors determine the different rates of regrowth in the P.N.S. and C.N.S. respectively? Implications are biological as well as clinical. If the fundamental biology of neurons is the same, whether in the C.N.S. or not, it may be surmised that local cytological interactions (rather than an intrinsic property of the cell body) determine the growth potential of a nerve process, such as the axon of an anterior horn cell. The theme for this proposal is a concerted study of interactions between collateral nerve sprouts and all related cells, including glia and Schwann cells, in the central and peripheral nervous systems, using the electronmicroscope. The Murray and Thompson model, demonstrating cytological relationships in the P.N.S. will be used as a basis for comparison with model situations in the C.N.S., starting with the medial septal nucleus. Use of the Murray and Thompson model has clarified ultrastructural features of sprouts and sheaths, indicated elements responsive to N.G.F. in vivo, and demonstrated dendritic expansions. Effects of N.G.F. and deafferentation on these expansions are being studied. In the C.N.S. model chosen, the objectives will be (1) to induce collateral formation and then (2) make a detailed study of cellular interrelationships and all observable "plastic changes," using montages to study these features after different survival periods. To understand better the ultrastructural correlates of mechanisms that determine the rate and extent of the plastic response, these studies must be extended to other C.N.S. models including sites where the response is reportedly minimal. Detailed observations and comparisons of plastic responses and cellular interactions will be made in all areas studied, to obtain clues about the regulatory mechanisms responsible for the differences.